Evidence map›Paper›PMID 40739755›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

CD93 blockade overcomes sunitinib resistance in pancreatic neuroendocrine tumors.

Yi Sun, Yuki Fujiwara, Robert J Torphy, Elliott J Yee, Yujie Guo, Zhiwei Sun, Junyi Hu, Eleanor Eck, Taichi Terai, Richard D Schulick and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Generative AI-drivenAntibody therapeutics · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yi SunDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Yuki FujiwaraDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Robert J TorphyDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Elliott J YeeDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Yujie GuoDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Zhiwei SunDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Junyi HuDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Eleanor EckDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Taichi TeraiDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Richard D SchulickDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Yuwen ZhuDivision of Surgical Oncology, Department of Surgery, the University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: yuwen.zhu@cuanschutz.edu.

Funding

The CD93 pathway and melanoma therapyR01CA258302 · NCI · UNIVERSITY OF COLORADO DENVER · PI Yuwen Zhu · 2022 to 2026
$1.8M
Melanoma Immunotherapy with GPR182 blockadeR01CA269644 · NCI · UNIVERSITY OF COLORADO DENVER · PI Yuwen Zhu · 2023 to 2026
$1.4M
The GPR171 pathway in cancer immunotherapyR01CA279398 · NCI · UNIVERSITY OF COLORADO DENVER · PI Yuwen Zhu · 2023 to 2026
$1.4M
NCI NIH HHS R01 CA258302NCI NIH HHS R01 CA269644NCI NIH HHS R01 CA279398
6 · The paper itself

Abstract

Pancreatic neuroendocrine tumors (PanNETs) are rare malignancies of the pancreas, but their incidence is steadily increasing. Standard therapy with antiangiogenic inhibitors, including sunitinib, has shown clinical benefit for advanced PanNETs; however, its long-term effectiveness is limited due to the development of resistance. In this study, we demonstrate that targeting the CD93-IGFBP7 axis enhances the efficacy of sunitinib by normalizing tumor vasculature in PanNETs. Both CD93 and its ligand IGFBP7 are enriched in the tumor microenvironment (TME) of PanNETs. Disrupting the CD93/IGFBP7 interaction with monoclonal antibodies (mAbs) in RIP1-Tag2 mice normalizes tumor vasculature to inhibit tumor progression and metastasis. Combining anti-CD93 mAb and sunitinib synergistically slows tumor growth and improves survival. Mechanistically, CD93 blockade mitigates sunitinib-induced tumor hypoxia and invasiveness, preventing the upregulation of proangiogenic factors. Critically, anti-CD93 mAb treatment prolongs survival in RIP1-Tag2 mice with late-stage, sunitinib-resistant PanNETs. Our results support CD93 blockade as a promising therapeutic approach for advanced PanNETs.

Indexed as

Drug Resistance, NeoplasmMembrane GlycoproteinsNeuroendocrine TumorsPancreatic NeoplasmsSunitinibAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalCell Line, TumorDisease Models, AnimalHumansMiceTumor MicroenvironmentXenograft Model Antitumor AssaysAngiogenesis InhibitorsAntibodies, MonoclonalMembrane GlycoproteinsSunitinibantiangiogenicCD93 blockadeIGFBP7pancreatic neuroendocrine tumorsunitinibtumor hypoxiavascular normalization

Identifiers

PMID40739755
PMCPMC12359193

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.